Inhibition of Breast Cancer Angiogenesis and Metastasis ay Targeting Hypoxia-Inducible Factor-1α

Abstract

DEDICATION"To (God) who is able to do immeasurably more than all we ask or imagine, according to his power that is at work within us"-Ephesians 3:20.And to my family-my wife, Pamela; and my children, Chinua and Elechi. For all you did to sustain my choice. Without you, this will not be.iv ACKNOWLEDGEMENTS I observe this dissertation today not as a completion of a search, but a celebration of success; symbolizing a temporary end as well as a beginning-signifying an achievement as well as triumph.This project culminating into this dissertation would not have been possible if it were not for the contributions and assistance I received from several people. In an attempt to express my appreciation, it will be very difficult to find words that have not already been used over again-a situation where statements will seem no longer sufficient and words inadequate. However I still wish to acknowledge the following persons who stood by me and contributed to make this long-nursed dream a reality.I would like thank my mentor, Dr Yi Lu, for the opportunity to work in his lab, and supervising this project. To my committee members, Dr Wei Li (for providing the compounds used in this project), Dr Leonard Lothstein (for his input, valuable discussions, and accessibility; for listening and reassuring), Dr Ram I Mahato (for his kind words of encouragement and permitting me to use his lab equipment), Dr Andrzej T Slominski (for his wise suggestions). Thank you for accepting to serve as members of this committee, your thoughtful criticism, and involvement during the course of this project. I would like to thank Dr liyuan Li for the lab training. I gratefully acknowledge Dr Pfeffer for his advice, and unending encouragement and support.My mother merits special thanks for her support and sacrifice through the years. So does my father-in-law, Obong Okon Mkpong, for his prayers and encouragement. Sufficient words fail me in expressing my gratitude to my wife, Eno-Obong Pamela, whose love, dedication, and relentless confidence in me was the driving force behind all of this. You are the bedrock upon which the past twelve years of my life have been built. My ambition was great, but your faith in me was greater. I love you dearly! To my children Chinua and Elechi, for their love, and understanding during the long years of my education, and sacrificially spending three summers with me in the lab-I promise, this is it! This project would never have been completed without the encouragement and devotion of all of you, and so many other family members and friends. In the words of President John F. Kennedy, "In your hands, more than mine, rest the final success of (my) course". Thank you! v ABSTRACTThe current clinical chemotherapy agents are not ideal for breast cancer as they are not curative, but only provide a modest extension of survival with sometimes a severely adverse effect on the patient's quality of life. There is, therefore, an urgent need to search for new and more effective anti-breast cancer drugs. However, the existing screening sy...